Psychoplastogenic DYRK1A Inhibitors with Therapeutic Effects Relevant to Alzheimer's Disease.

Tauopathy, neuronal atrophy, and psychological impairments are hallmarks of neurodegenerative diseases, such as Alzheimer's disease, that currently lack efficacious clinical treatments capable of rectifying these issues. To address these unmet needs, we used rational drug design to combine the pharmacophores of DYRK1A inhibitors and isoDMTs to develop psychoplastogenic DYRK1A inhibitors. Using this approach, we discovered a nonhallucinogenic compound capable of promoting cortical neuron growth and suppressing tau hyperphosphorylation while also having the potential to mitigate the biological and psychological symptoms of dementia.

Comparing the clinical utility of the alternative model for personality disorders to the Section II personality disorder model: A randomized controlled trial.

The alternative model for personality disorders (AMPD) has been extensively studied over the past decade, but to date there is no direct comparison of the clinical utility of the AMPD model relative to the Section II personality disorder (PD) model in an ecologically valid design. The current study examined the clinical utility of an AMPD-informed assessment procedure and Section II PD assessment procedure as assessed by both patients and clinicians in a randomized controlled trial. A sample of 119 patients were randomly assigned to either an AMPD or a Section II PD assessment procedure.

5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines.

Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns and limit their clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding of how these molecules produce therapeutic effects.

Psychedelic-inspired approaches for treating neurodegenerative disorders.

Psychedelics are increasingly being recognized for their potential to treat a wide range of brain disorders including depression, post-traumatic stress disorder (PTSD), and substance use disorder. Their broad therapeutic potential might result from an ability to rescue cortical atrophy common to many neuropsychiatric and neurodegenerative diseases by impacting neurotrophic factor gene expression, activating neuronal growth and survival mechanisms, and modulating the immune system. While the therapeutic potential of psychedelics has not yet been extended to neurodegenerative disorders, we provide evidence suggesting that approaches based on psychedelic science might prove useful for treating these diseases.

An expanded auxin-inducible degron toolkit for Caenorhabditis elegans.

The auxin-inducible degron (AID) system has emerged as a powerful tool to conditionally deplete proteins in a range of organisms and cell types. Here, we describe a toolkit to augment the use of the AID system in Caenorhabditis elegans. We have generated a set of single-copy, tissue-specific (germline, intestine, neuron, muscle, pharynx, hypodermis, seam cell, anchor cell) and pan-somatic TIR1-expressing strains carrying a co-expressed blue fluorescent reporter to enable use of both red and green channels in experiments.

The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of spermatogenesis.

In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulating molting, we discovered that NHR-23/NR1F1 is also constitutively expressed in developing primary spermatocytes and is a critical regulator of spermatogenesis.

Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a non-randomized, monocentric phase II clinical trial-PaCa-DD-041 (Eudra-CT 2009-011968-11).

Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of 20-25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor.

Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer.

Background: Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection.

Methods: One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated.

The pathohistological subtype strongly predicts survival in patients with ampullary carcinoma.

Ampullary cancer represents approximately 6% of the malignant periampullary tumors. An early occurrence of symptoms leads to a 5-year survival rate after curative surgery of 30 to 67%. In addition to the tumor stage, the immunohistological subtypes appear to be important for postoperative prognosis.

The impact of surgical experience and frequency of practice on perioperative outcomes in pancreatic surgery.

Objective: We aimed to determine the impact of surgical experience and frequency of practice on perioperative morbidity and mortality in pancreatic surgery.

Methods: 1281 patients that underwent pancreatic resections from 1993 to 2013 were retrospectively analyzed using logistic regression models. All cases were stratified according to the surgeon's level of experience, which was based on the number of previously performed pancreatic resections and the extent of received supervision (novice: n <  20 / intensive; intermediate: n = 21-90 / decreasing; and experienced surgeon: n > 90 / none).

Validation of prognostic risk scores for patients undergoing resection for pancreatic cancer.

Background/objectives: A better stratification of patients into risk groups might help to select patients who might benefit from more aggressive therapy. The aim of this study was to validate five prognostic scores in patients resected for pancreatic ductal adenocarcinoma (PDAC).

Methods: Included were 307 PDAC patients who underwent resection with curative intent.

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.

Aims/hypothesis: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.

Para-aortic lymph node metastases in pancreatic cancer should not be considered a watershed for curative resection.

No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005-2015. In 95 cases, the PALN were separately labelled and histopathologically analysed.

Assessing DSM-5-oriented level of personality functioning: Development and psychometric evaluation of the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1).

The alternative model for personality disorders (AMPD) in the () features a Level of Personality Functioning Scale, measuring intrinsic personality processes that include identity, self-direction, empathy, and intimacy. This study describes the development and psychometric evaluation of a semistructured interview schedule for the multi-item assessment of the level of personality functioning, the Semi-Structured Interview for Personality Functioning (STiP-5.1).

Impact of Portal Vein Involvement from Pancreatic Cancer on Metastatic Pattern After Surgical Resection.

Background: The present study aims to evaluate the long-term outcome and metastatic pattern of patients who underwent resection of a pancreatic ductal adenocarcinoma (PDAC) with portal or superior mesenteric vein (PV/SMV) resection.

Methods: Patients who underwent a partial pancreatoduodenectomy or total pancreatectomy for PDAC between 2005 and 2015 were retrospectively analyzed. Three subgroups were generated, depending on PV/SMV resection (P) and pathohistological PV/SMV tumor infiltration (I): PI, PI, and PI.

Treatment of tailgut cysts by extended distal rectal segmental resection with rectoanal anastomosis.

Purpose: Complete surgical resection is the treatment of choice for tailgut cysts, because of their malignant potential and tendency to regrow if incompletely resected. We report our experience of treating patients with tailgut cysts, and discuss diagnostics, surgical approaches, and follow-up.

Methods: We performed extended distal rectal segmental resection of the tailgut cyst, with rectoanal anastomosis.

Impact of Intraoperative Re-resection to Achieve R0 Status on Survival in Patients With Pancreatic Cancer: A Single-center Experience With 483 Patients.

Objective: The aim of this study was to test the hypothesis that intraoperative frozen section (FS) and re-resection results to achieve R0 status are associated with different long-term outcomes in pancreatic cancer patients.

Background: Recent data have challenged the survival benefit of additional resection in patients with pancreatic cancer in case of positive FS to achieve clear pathological section (PS).

Methods: Patients who underwent surgery for exocrine pancreatic malignancy with curative intent were identified from a prospective database.

Memorable Experiences in Therapeutic Assessment: Inviting the Patient's Perspective Following a Pretreatment Randomized Controlled Trial.

Accumulating evidence documents the efficacy of Therapeutic Assessment (TA) in terms of symptom reduction and other outcomes, but only minimal data speak to the patient's perspective of what is memorable, or potentially important, about this intervention. In line with the humanistic and phenomenological philosophy of TA, we solicited patient input by asking personality disorder (PD) patients who participated in a recent randomized controlled trial (De Saeger et al., 2014 ) about their experiences.

Evaluation of central pancreatectomy and pancreatic enucleation as pancreatic resections--A comparison.

Introduction: For minor pancreatic resection such as enucleation (PE) and central pancreatectomy (CP) comparative data are rare. These techniques provide parenchyma-sparing alternatives to major resections (e.g.

Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis.

Background And Aim: Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables.

Methods: In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial.

Measurement of DSM-5 section II personality disorder constructs using the MMPI-2-RF in clinical and forensic samples.

In the current study, we evaluated the associations between the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) scale scores and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) Section II personality disorder (PD) criterion counts in inpatient and forensic psychiatric samples from The Netherlands using structured clinical interviews to operationalize PDs. The inpatient psychiatric sample included 190 male and female patients and the forensic sample included 162 male psychiatric patients.

Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy.

Background: There is an ongoing debate about the best closure technique after distal pancreatectomy (DP). The aim of the closure is to prevent the formation of a clinically relevant post-operative pancreatic fistula (POPF). Stapler technique seems to be equal compared with hand-sewn closure of the remnant.

Future perspectives for surgical research in Germany.

Background: During the last two decades, the complexity of surgical patient care has increased dramatically. Nonetheless, there is substantial need to improve the quality of surgical research in Germany.

Purpose: Herein, we present the current concepts of the German Society of Surgery, the Section of Surgical Research, the Study Center of the German Surgical Society, and the German Surgical Trial Network (CHIR-Net) and their perspectives to promote young surgeons for a career in academic surgery and to improve the quality of surgical research in experimental studies as well as in clinical trials.

Therapeutic assessment promotes treatment readiness but does not affect symptom change in patients with personality disorders: findings from a randomized clinical trial.

The field of clinical personality assessment is lacking in published empirical evidence regarding its treatment and clinical utility. This article reports on a randomized controlled clinical trial (N = 74) allocating patients awaiting treatment in a specialized clinic for personality disorders to either 4 sessions of (a) therapeutic assessment (TA) or (b) a structured goal-focused pretreatment intervention (GFPTI). In terms of short-term outcome, TA demonstrated superior ability to raise outcome expectancies and patient perceptions of progress toward treatment (Cohen's d = 0.